Rare variant recall study (Version 1)
Research type
Research Study
Full title
Molecular and clinical characterization of rare genetic variation focusing on individuals of South Asian ancestry
IRAS ID
275115
Contact name
Shwetha Ramachandrappa
Contact email
Sponsor organisation
Queen Mary University of London
Duration of Study in the UK
4 years, 11 months, 30 days
Research summary
"Research Summary"
We all carry a large number of genetic variants, that is, there are specific parts of our genetic code which are different from the general population. Most genetic variants are harmless. Some genetic variants called loss of function variants can prevent the gene the variant falls within from functioning properly. It is difficult to tell which variants are going to affect gene function, and which are not.We each have two copies of most genes inheriting one from our mother and one from our father. If they each contain a loss of function variant then this leads to the corresponding gene being "knocked out". We know that individuals with variants causing a gene knockout are more frequent in certain parts of the world where a population has been geographically or socially isolated. The same is true of communities where there are increased levels of parental relatedness.
In this study we will analyze genetic data, electronic health record data and clinical data to characterize a large number of naturally occurring gene knock outs. This work will initially focus on relatively healthy volunteers of South Asian ancestry. Where it is deemed useful, feasible and acceptable, individuals from other sources will be recruited.
We intend to generate a bio-resource of patient derived materials to enable cellular level and organism level phenotypes to be studied side by side. The detailed characterization of rare variants in this way is likely to yield novel insights into gene structure, function and redundancy across a broad range of disease areas. This work is also likely to help us identify genes which can be safely and effectively used as therapeutic targets.
As a parallel stream of work questionnaire based tools will be developed to gauge the level of genetic literacy amongst participants. This will be key to long term community engagement.
"Summary of results"
This study intended to look at individuals who have been found to carry rare homozygous genetic variants in genes which have been associated with human diseases. Participants were going to be identified from the Genes and Health study. The objectives of the study were to understand the clinical manifestations of the rare genetic variants that we identified and to develop assays to understand the impact of these variants at a molecular level.We intended to recruit 300 people to the study. Due to numerous recruitment issues only 9 people were recruited to this study. There were no adverse events. The UK Policy Framework for Health and Social care research, GCP and the protocol were adhered to throughout.
In view of the small numbers of participants there are no results from this study and nothing to feedback to participants or to publish. All biological samples collected as part of this study have been destroyed in accordance with the protocol.
REC name
Wales REC 7
REC reference
21/WA/0396
Date of REC Opinion
10 Jan 2022
REC opinion
Further Information Favourable Opinion